We hypothesize that underlying susceptibility gene (s) are critical to the development of age-related macular degeneration (AMD) and that they most likely interact with environmental factors to trigger the development and progression of this disease. We propose a multi-pronged approach to the identification of susceptibility gene(s) for age-related macular degeneration (AMD). During the initial grant period we developed a large genetic AMD database including large families and multiplex families with affected sib-pairs, and have identified several areas of genetic linkage to pursue. During the next grant period, we propose a multipronged approach to build upon this database, with the goal of finding the gene or genes associated with AMD susceptibility. We will use family-based and population-based case-control association studies, combined with an expanded genome-wide sib-pair study for this project. Single nucleotide polymorphisms in high priority positional or functional AMD candidate loci will be genotyped for the association studies and linkage disequilibrium and transmission disequilibrium tests will be performed. Sib-pair linkage analysis using both quantitative and qualitative traits on the expanded genome-wide scan will be completed. We will collect family history and risk factor data and conduct studies examining these risk factors for AMD. These data will provide important information to analyze the influence of environmental factors as information about specific genetic factors involved in the disease is identified. This study should provide important new information about the etiology of AMD which is the leading cause of irreversible blindness among elderly individuals worldwide, so that preventative or treatment measures can be developed. [unreadable] [unreadable] [unreadable] [unreadable]